| US 7,446,123 B2 | ||
| Azabicyclo derivatives as muscarinic receptor antagonists | ||
| Mohammad Salman, Plainsboro, N.J. (US); Anita Mehta, Plainfield, Ill. (US); Pakala Kumara Savithru Sarma, Haryana (India); Naresh Kumar, Haryana (India); Sankaranarayanan Dharmarajan, Haryana (India); Kirandeep Kaur, Haryana (India); and Anita Chugh, Delhi (India) | ||
| Assigned to Ranbaxy Laboratories Limited, Gurgaon, Haryana (India) | ||
| Appl. No. 10/552,455 PCT Filed Jan. 07, 2004, PCT No. PCT/IB2004/000012 § 371(c)(1), (2), (4) Date Jan. 14, 2008, PCT Pub. No. WO2004/089364, PCT Pub. Date Oct. 21, 2004. |
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| Claims priority of application No. PCT/IB03/01367 (WO), filed on Apr. 11, 2003. | ||
| Prior Publication US 2006/0287380 A1, Dec. 21, 2006 | ||
| Int. Cl. A61K 31/40 (2006.01); A61K 31/4035 (2006.01); C07D 209/52 (2006.01); C07D 209/52 (2006.01) | ||
| U.S. Cl. 514—412 [548/452; 548/470; 548/515; 514/416] | 2 Claims |
| 1. A compound selected from:
(2R,2S)(1α,5α,6α)-N-{-[4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butyl]-3-azabicyclo[3.1.0]hex-6-yl-methyl}-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(Compound No. 1);
(2R)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopent-1-enyl-2-phenylacetamide (Compound No.
2);
(2R,2S)(1α,5α,6α)-N-(3-Isopropyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.
3);
(2R,2S)(1α,5α,6α)-N-(3-Diphenylmethyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound
No. 4);
(2R,2S)(1α,5α,6α)-N-(3-sec-butyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound No.
5);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(3-pentyl)-2-phenylacetamide (Compound No. 6);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclohexyl-2-(4-methoxyphenyl)acetamide (Compound
No. 7);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-phenyl-(N-ethyl)-2-phenylacetamide (Compound
No. 8);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-(N-ethyl)-2-phenylacetamide (Compound
No. 9);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclohexyl-(N-ethyl)-2-phenylacetamide (Compound
No. 10);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(3-pentyl)-(N-methyl)-2-phenylacetamide (Compound
No. 11);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(sec-butyl)-(N-methyl)-2-phenylacetamide (Compound
No. 12);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-isopropyl-(N-methyl)-2-phenylacetamide (Compound
No. 13);
(2R,2S)(1α,5α,6α)-N-[3-(4-tert-butyl-benzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide
(Compound No. 14);
(2R,2S)(1α,5α,6α)-N-(3-Benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclohex-2-enyl-2-phenylacetamide (Compound
No. 15);
(2R,2S)(1α,5α,6α)-N-[3-(4-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2,2-diphenylacetamide (Compound No.
16);
(2R,2S)(1α,5α,6α)-N-[3-(4-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound
No. 17);
(2R,2S)(1α,5α,6α)-N-[3-(4-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound
No. 18);
(2R,2S)(1α,5α,6α)-N-[3-(3-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2,2-diphenylacetamide (Compound No.
19);
(2R,2S)(1α,5α,6α)-N-[3-(3-fluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2,2-diphenylacetamide (Compound No.
20);
(2R,2S)(1α,5α,6α)-N-[3-(3-fluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound
No. 21);
(2R,2S)(1α,5α,6α)-N-[2-(2,4-difluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclohexyl-2-phenylacetamide (Compound
No. 22);
(2R,2S)(1α,5α,6α)-N-[3-(2,4-difluorobenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2,2-diphenylacetamide (Compound
No. 23);
(2R,2S)(1α,5α,6α)-N-[3-(3-methylbenzyl)-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound
No. 24);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(4-methylphenyl)-2-phenylacetamide (Compound
No. 25);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(4-methylphenyl)-(N-methyl)-2-phenylacetamide
(Compound No. 26);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(4-fluorophenyl)-2-phenylacetamide (Compound
No. 27);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(4-fluorophenyl)-2-phenyl acetic acid ester (Compound
No. 28);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(4-fluorophenyl)-(N-methyl)-2-phenylacetamide
(Compound No. 29);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(3-methylphenyl)-2-phenylacetamide (Compound
No. 30);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(3-methylphenyl)-(N-methyl)-2-phenylacetamide
(Compound No. 31);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-(3-methylphenyl)-2-phenyl acetic acid ester (Compound
No. 32);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-(3-methylphenyl) acetic acid ester
(Compound No. 33);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-(3-methylphenyl) acetic acid ester
tartarate salt (Compound No. 34);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-(3-methylphenyl)acetamide (Compound
No. 35);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-(3-methylphenyl)acetamide tartarate
salt (Compound No. 36);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2,2-di(4-fluorophenyl)acetic acid ester (Compound
No. 37);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2,2-di(4-fluorophenyl)-acetamide (Compound No.
38);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclobutyl-2-phenyl acetic acid ester (Compound
No. 39);
(2R,2S)(1α,5α,6α)-N-(3-cyclohexylmethyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-2-phenylacetamide (Compound
No. 40);
(2R)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-cyclopentyl-(N-methyl)-2-phenylacetamide (Compound
No. 41);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-cyclopentyl-2-(4-methylphenyl)acetamide (Compound
No. 42);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-phenyl-2-(4-methylphenyl) acetic acid ester (Compound
No. 43);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-methyl-2-phenyl acetic acid ester (Compound No.
44);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-methyl-2-phenyl acetamide (Compound No. 45);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-isopropyl-2-phenyl acetic acid ester (Compound
No. 46);
(2R,2S)(1α,5α,6α)-N-(3-methyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-phenyl-(N-methyl)-2-phenylacetamide (Compound
No. 47);
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-(3-methylphenyl)-2-(3-methylphenyl)acetamide
(Compound No. 48);
(2R,2S)(1α,5α,6α)-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl]-2-hydroxy-2-(3-pentyl)-2-phenyl acetic acid ester (Compound
No. 49); and
(2R,2S)(1α,5α,6α)-N-(3-benzyl-3-azabicyclo[3.1.0]hex-6-yl-methyl)-2-hydroxy-2-methyl-(N-methyl)-2-phenylacetamide (Compound
No. 50).
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